The proposed biomechanical studies continue our multi-disciplinary group's attempts to build an engineering-based characterization of the principal components of ONH susceptibility to glaucomatous damage. They test the following Hypotheses regarding the effects of intraocular pressure (IOP) within the first finite element models (FEMs) of the load-bearing connective tissues of the optic nerve head (ONH): 1) The distribution of stress (force/cross-sectional area) and strain (local deformation) within the lamina cribrosa and scleral canal of the normal ONH predicts the sites of connective tissue damage in early experimental glaucoma. 2) At all levels of IOP, stresses and strains within the remaining connective tissues of early and moderate glaucoma eyes are higher than in normal eyes. 3) Fixed deformation of the connective tissues underlies the onset and progression of glaucomatous cupping in early and moderate glaucoma ONH but is not significantly present in early and late ONH ischemia. 4) The ONH and peripapillary connective tissues of older eyes are less elastic than those of younger eyes. The Specific Aims and Objectives are: 1) To expand the resolution and accuracy of the existing continuum FEMs of normal and early glaucomatous ONH by introducing anisotropric, bi-axial material properties and voxel-based finite elements; 2) To extend the modeling to moderate glaucomatous damage; 3) To make measurements within the digital 3D geometries of normal, early and moderate glaucomatous, and early and late endothelin-treated, ischemic ONH so as to characterize and compare the 3D patterns of connective tissue damage; 4) To compare ONH connective tissue deformation and bi-axial posterior scleral material properties in young and old eyes. The Methodology includes compliance testing of the ONH surface; bi-axial tensile testing of the intact posterior scleral shell; construction of digital 3D geometries of the ONH connective tissues from serial color images of the embedded tissue block surface after serial 3-um sectioning; and continuum, micro finite element, and hybrid finite element modeling of the load-bearing connective tissues of the ONH.